The LC3-conjugation machinery specifies the loading of RNA-binding proteins into extracellular vesicles.
Nat Cell Biol
; 22(2): 187-199, 2020 02.
Article
in En
| MEDLINE
| ID: mdl-31932738
ABSTRACT
Traditionally viewed as an autodigestive pathway, autophagy also facilitates cellular secretion; however, the mechanisms underlying these processes remain unclear. Here, we demonstrate that components of the autophagy machinery specify secretion within extracellular vesicles (EVs). Using a proximity-dependent biotinylation proteomics strategy, we identify 200 putative targets of LC3-dependent secretion. This secretome consists of a highly interconnected network enriched in RNA-binding proteins (RBPs) and EV cargoes. Proteomic and RNA profiling of EVs identifies diverse RBPs and small non-coding RNAs requiring the LC3-conjugation machinery for packaging and secretion. Focusing on two RBPs, heterogeneous nuclear ribonucleoprotein K (HNRNPK) and scaffold-attachment factor B (SAFB), we demonstrate that these proteins interact with LC3 and are secreted within EVs enriched with lipidated LC3. Furthermore, their secretion requires the LC3-conjugation machinery, neutral sphingomyelinase 2 (nSMase2) and LC3-dependent recruitment of factor associated with nSMase2 activity (FAN). Hence, the LC3-conjugation pathway controls EV cargo loading and secretion.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
/
RNA-Binding Proteins
/
Extracellular Vesicles
/
Autophagosomes
/
Microtubule-Associated Proteins
Type of study:
Prognostic_studies
Language:
En
Journal:
Nat Cell Biol
Year:
2020
Document type:
Article
Affiliation country:
United States